Lim, Seungho Kim, Woojun Song, Sukyung Shim, Man Kyu Yoon, Hong Yeol Kim, Byung-Soo Kwon, Ick Chan Kim, Kwangmeyung 2024-01-19T15:32:52Z 2024-01-19T15:32:52Z 2021-09-02 2021-01-20 1043-1802 https://pubs.kist.re.kr/handle/201004/117511 Nanoparticles have been used for effectively delivering imaging agents and therapeutic drugs into stem cells. However, nanoparticles are not sufficiently internalized into stem cells; thus, new delivery method of nanoparticles into stem cells is urgently needed. Herein, we develop bicyclo[6.1.0]nonyne (BCN)-conjugated gold nanoparticles (BCN-AuNPs), which can be bioorthogonally conjugated to azide (-N-3) groups on the surface of metabolically engineered stem cells via bioorthogonal click chemistry. For incorporating azide groups on the cell surface, first, human adipose-derived mesenchymal stem cells (hMSCs) were metabolically engineered with N-azidoacetylmannosamine-tetraacylated (Ac(4)ManNAz). Second, clickable BCN-AuNPs were bioorthogonally conjugated to azide groups on Ac(4)ManNAz-treated hMSCs. Importantly, a large amount of BCN-AuNPs was specifically conjugated to metabolically engineered hMSCs and then internalized rapidly into stem cells through membrane turnover mechanism, compared to the conventional nanoparticle-derived endocytosis mechanism. Furthermore, BCN-AuNPs entrapped in endosomal/lysosomal compartment could escape efficiently to the cytoplasm of metabolically engineered stem cells. Finally, BCN-AuNPs in stem cells were very safe, and they did not affect stem cell functions, such as self-renewal and differentiation capacity. These bioorthogonally conjugated nanoparticles on metabolically engineered stem cells can enhance the cellular uptake of nanoparticles via bioorthogonal conjugation mechanism. English AMER CHEMICAL SOC MESOPOROUS SILICA NANOPARTICLES FREE CLICK CHEMISTRY CELLULAR UPTAKE GOLD NANOPARTICLES OSTEOGENIC DIFFERENTIATION QUANTUM DOTS PROTEIN TRACKING MEMBRANE ENDOSOME Intracellular Uptake Mechanism of Bioorthogonally Conjugated Nanoparticles on Metabolically Engineered Mesenchymal Stem Cells Article 10.1021/acs.bioconjchem.0c00640 1 BIOCONJUGATE CHEMISTRY, v.32, no.1, pp.199 - 214 BIOCONJUGATE CHEMISTRY 32 1 199 214 scie scopus 000612551500021 2-s2.0-85100173398 Biochemical Research Methods Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry, Organic Biochemistry & Molecular Biology Chemistry Article MESOPOROUS SILICA NANOPARTICLES FREE CLICK CHEMISTRY CELLULAR UPTAKE GOLD NANOPARTICLES OSTEOGENIC DIFFERENTIATION QUANTUM DOTS PROTEIN TRACKING MEMBRANE ENDOSOME